Progesterone Microspheres Pharmacokinetic - Pharmacodynamic (PK-PD) Study

Randomized, Controlled, Open-label, Parallel, Clinical Trial to Assess Pharmacokinetics and Endometrial Effect of an Injectable Formulation of Progesterone Microspheres in Doses of 50 mg, 100 mg, 200 mg and 300 mg, in Postmenopausal Women.

Phase: I pharmacokinetic - pharmacodynamic (PK-PD) study. Main objective: To establish the minimum effective dose of progesterone microspheres suspension, which administered by weekly intramuscular injection, will be able to induce transformation from a proliferative endometrium to a secretory endometrium.

Study design: Randomized, controlled, open-label, parallel, dose-response clinical trial.

Sites: 1 Subjects: 48 postmenopausal women.

Sites: 1 Phase: 1 Main objective:To establish the minimum effective dose of progesterone microspheres suspension, which administered by weekly intramuscular injection, will be able to induce transformation from a proliferative endometrium to a secretory endometrium.

Secondary objectives:

• To determine and compare the steady-state pharmacokinetic profile of investigational products.
• To evaluate safety profile of investigational products in the study subjects.
• To evaluate local tolerability of investigational products in the study subjects.

Study design:Randomized, controlled, open-label, parallel, dose-response clinical trial.

Investigational products:

• Progesterone microspheres intramuscular injectable suspension 50 mg
• Progesterone microspheres intramuscular injectable suspension 100 mg
• Progesterone microspheres intramuscular injectable suspension 200 mg
• Progesterone microspheres intramuscular injectable suspension 300 mg Study subjects: 48 healthy postmenopausal women, 45 - 60 years. Brief description: After written informed consent, 48 eligible women will receive pretreatment with oral estradiol valerate, then, 14 days later, those with adequate endometrial thickness evaluated through ultrasound will be randomized to study treatments (one IM injection each 7 days, for a total of 7 doses). 10 days after the first progesterone dose, an endometrial biopsy will be obtained. Blood samples will be obtained for pharmacokinetic study.

Inclusion Criteria:

• Female
• 45 to 60 years old
• Able to read and write
• Postmenopausal
• Body Mass Index equal or below 34.99 kg/m2
• Healthy
• Normal uterus
• Time availability

Exclusion Criteria:

• Hypersensitivity to progesterone or related compounds
• Hypersensitivity to estrogens
• Hysterectomy
• History or present hormone-dependent tumor
• History or present uterine cervix dysplasia
• Abnormal and clinically-significant laboratory test results
• Family history of breast cancer
• History of thromboembolic disease
• Non-controlled hypertension
• History of stroke
• History of cardiac valve surgery
• Renal failure
• Hepatic failure
• Non-controlled diabetes
• Severe gastrointestinal disease
• History of serious neurologic disease
• Reduced mobility
• Anemia
• Previous or concomitant hormonal therapy
• Previous or concomitant therapy with inhibitors or inductors of cytochrome